Cellular differentiation from human lung epithelial progenitor cells to pulmonary nuroendocrine cells

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Lung epithelial neuroendocrine cells are differenciated from multipotent stem cell in lung at the mid term of the pregnancy in human. Pulmonary neuroendocrine cells secret catecholamine and neural peptides, resulting in the regulation of the proliferation and differentiation of lung epithelial cells. It could be possible that neuroendocrine cell differentiation may be associate to pathogenesis of lung diseases. We hypothesized that Ash1 might modulate the differentiation of neuroendocrine cell. To understand the mechanism of pulmonary neuroendocrine cell, we established the in virto cell culture system in which multi-potent stem cell of lung epithelium can differentiate to neuroendocrine-like cells. Interaction collagen matrix and hypoxic condition are important conditions that differentiate the premature pulmonary epithelial cells to neuroendocrine cells. Gene expression profiles under cell differentiation indicated that biphasic up-regulation of Ash1 might be critical for the determination of the epithelial cells for the neuroendocrine differentiation. In these processes, Ash1 regulated the target genes. To assess the role of Ash1 in this process, we tried to produce SiRNA to knockdown Ash1 mRNA. Knockdown of Ash1 expression repressed the cellular differentiation of progenitor cells to neuroendocrine cells and repress typrosine hydroxylase transcription. Our research, now, is ongoing to identify the mechanism of Ash1-regulated gene expression with association to the pulmonary neuroendocrine cell differentiation.